Dimethylformamide → 3-Bromo-8-chloro-1,5-naphthyridine

HRID 40371Notes

Reaction equation

HRID 40371 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[CH:7]=[CH:8][NH:9]2)=[N:4][CH:3]=1.CN(C=O)C.C(Cl)(=O)C([Cl:21])=O.C(=O)(O)[O-].[Na+]>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[N:9][CH:8]=[CH:7][C:6]=2[Cl:21]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 134591367-Bromo-1,5-naphthyridin-4-ol

Product 1

HCID 134591373-Bromo-8-chloro-1,5-naphthyridineYield 14%

Conditions

Temperature
95 °C

Procedure

7-bromo-1,5-naphthyridin-4(1H)-one (23.8 g, 105.8 mmol), acetonitriel (192 mL, 105.8 mmol), and DMF (2.05 mL, 26.5 mmol) were placed in a 3-necked round bottom flask set up with a reflux condenser. Argon bubbled through. Reaction mixture brought to reflux (˜95° C.). Oxalyl chloride (28.7 ml, 328.1 mmol) was added dropwise via addition funnel over 40 minutes and reaction allowed to stir at this temperature for 16 hrs. Reaction mixture cooled to 0° C. and basified to pH ˜8 with aqueous sodium bicarbonate solution. Product extracted with DCM (500 mL) three times. Organic layers combined, dried over sodium sulfate and concentrated to afford brown solid. This was purified by ISCO silica gel chromatography to afford 3-bromo-8-chloro-1,5-naphthyridine (3.6 g, 14% yield) as fluffy tan solid.

Workup

  1. customset up with a reflux condenser
  2. customArgon bubbled through
  3. customReaction mixture
  4. customreaction
  5. customReaction mixture
  6. extractionProduct extracted with DCM (500 mL) three times
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customto afford brown solid
  10. customThis was purified by ISCO silica gel chromatography

Sources & evidence

ORD record
ord-b1eb66dc88a54693a18d71090b63290e
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Reaction notes

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